FMNL1 (formin-like protein 1) binds the active, GTP-bound, form of RAC1 (Yayoshi-Yamamoto et al. 2000). Based on the sequence similarity with mouse formin Dia1, binding of RAC1:GTP relieves the autoinhibition of FMNL1 by displacing the C-terminal autoregulatory DAD domain of FMNL1 from the N-terminal FH3 domain (Rose et al. 2005, Lammers et al. 2005). As formins dimerize through their FH2 domains, it is not clear whether the autoinhibitory interaction between FH3 and DAD domains is intramolecular or intermolecular (Xu et al. 2004, Kuhn and Geyer 2014). Endogenous human FMNL1 interacts with endogenous human RAC1 in some leukemia-derived cell lines and promotes their migration (Favaro et al. 2013). FMNL1 gamma, a transcriptional isoform of FMNL1 with a DAD domain that significantly differs in sequence from DAD domains of FMNL1 transcription isoforms alpha and beta, localizes to the membrane and is active in the absence of RHO GTPase signaling. The membrane localization of FMNL1 gamma is regulated by the myristoylation of the N-terminal glycine which is triggered by an unknown mechanism (Han et al. 2009).